Distribution of HLA-B*27 subtypes in Tunisians and their association with ankylosing spondylitis

ObjectiveThe human leukocyte antigen HLA-B27 is a class I antigen of the major histocompatibility complex strongly associated with ankylosing spondylitis (AS) and other related spondyloarthropathies (SpAs). The mechanism of this association remains unknown. HLA-B27 is a serologic specificity that represents a family of at least 25 different HLA-B27 alleles (2701–2725). These alleles are closely related by nucleotide sequence homology, but differ in ethnic distribution. The purpose of the present study is to investigate the distribution of HLA-B27 alleles in healthy controls and in patients with ankylosing spondylitis (AS).MethodsWe selected 160 HLA-B27-positive individuals (39 controls and 121 patients with ankylosing spondylitis). Typing of HLA-B27, and Cw alleles were performed by polymerase chain reaction amplification with sequence specific primers (PCR–SSP), and by serological typing (microlymphocytotoxicity).ResultsSeven B27 subtypes were identified: B*2702, 03, 04, 05, 07, 09 and B*2714. The distribution of these alleles in the population of patients was B*2702 (47.1%) and B*2705 (47.1%). These subtypes were also detected in 16 (41%) and 16 (41%), respectively of the 39 control subjects. HLA-B*2707 was detected in 4 (3.31%) patients and in 3 (7.6%) controls. B*2704, 09 and B*2714 were relatively rare and were detected in one subject each. No significant differences were noticed in the frequencies and distribution of HLA-B27 alleles between patients and controls.ConclusionsOur results show a restricted number of HLA B27 subtypes associated with AS. B*2702 and B*2705 were equally common in patients and controls. The most prominent B27/Cw haplotypes in the patient groups and controls were B*2702/Cw02022 and B*2705/Cw02022.     

Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12 deficiency with neurological symptoms

The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB₁₂) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B₁₂‐deficient patients (vit B₁₂ < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B₁₂ level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose‐dependent manner with HB₁₂. The apparent permeability of Hdrx was P_app = 34.9 ± 4.6 × 10^?6 cm/s in the presence of 3 mg/mL (HB₁₂B) compared to the control P_app = 6.2 ± 0.7 × 10^?6 cm/s. (ii) Total transepithelial electrical conductance (G_t) increased in dose‐dependent manner with HB₁₂, G_t = 161.5 ± 10.8 mS/cm² with HB₁₂B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, G_t = 28.7 ± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS.     

Hemifacial spasm and craniovertebral anomaly

Two patients with congenital anomaly of the craniovertebral junction causing disabling hemifacial spasm (HFS) are presented. In one patient, complete cessation of the HFS occurred for a period of two years following simple bony decompression of the craniovertebral junction raising unanswered questions as to the exact pathogenesis of HFS. Eventually both patients required microvascular decompression at the root entry zone of the facial nerve.     

Psychosexual and psychosocial sequelae of closed head injury

A series of 36 patients who had been hospitalized following closed head injury (CHI) were followed up 4.06 (SD 3.71) years after the injury. Measures were taken of degree of psychosexual dysfunction (Golombok Rust Inventory of Sexual Satisfaction-GRISS), general psychiatric morbidity (General Health Questionnaire-GHQ), and clinical anxiety and depression (Hospital Anxiety and Depression Scale-HAD). These measures were completed by patients and partners. Resulting data revealed that 50% of male patients with current sexual partners produced psychosexual profiles that fell within the dysfunctional range. For both male patients and their partners, the chief psychosexual complaint was infrequency. Of the patients studied, 61% were classified (using the GHQ) as having degrees of emotional distress that would fall within the range of psychiatric 'caseness', while 25% of patients achieved HAD criteria for clinical anxiety and 22% met HAD criteria for depression. Of the partners, 41% met GHQ criteria for psychiatric 'caseness', 18% being classified using the HAD as anxiety cases and 6% as depression cases. No effects of severity of injury were observed on any of the main outcome measures. Age and time since injury were related to measures of psychosexual dysfunction. These results are discussed in relation to the existing literature on psychosocial outcome in closed head injury, and recommendations for therapeutic intervention are made.     

Sequential Methotrexate, 5-Fluorouracil, and Leucovorin in Metastatic Measurable Colorectal Cancer. Does It Work?

Four single-arm trials using methotrexate (M), 5-fluomuracil (5FU), and leucovorin (L) were sequentially performed in metastastic measurable colorectal cancer using different dosing and timing schedules for the three drugs. A total of 99 patients were entered into the trials, 92 (49 men and 43 women) of whom were evaluable for response. Although the first trial appeared to have a 36% response rate, the overall response rate seen in the four trials was not higher than historical reports of 5FU alone. We could find no correlation with dose intensity or patient characteristics to account for the apparent good results of the first trial. It is our conclusion that MFL is not an active combination in colorectal cancer. After progressing to the fourth trial, four patients were placed on 5FU alone (supported by a grant from Lederle, Canada). This resulted in one response in a patient who had not responded to the three-drug combination and stable disease in two patients previously progressing. Although there are many reports of this combination working, the possibility is raised that M may be inhibitory to the combination despite the in vitro data.     

The effect of lonidamine alone and in combination with cisplatin on in vitro growth and viability of lung squamous cell carcinoma cell lines

Two non small cell lung cancer (NSCLC) cell lines were tested in vitro to evaluate the effect of lonidamine, cisplatin and combinations of these two agents using different doses and schedules. Lonidamine alone at concentrations greater than 50 micrograms/ml caused inhibition of cell growth in both monolayer and spheroid cell cultures. Cisplatin at concentrations of 10-20 microM caused a concentration dependent toxicity and inhibited growth in monolayer and spheroid cell cultures. Combination treatment of lonidamine and cisplatin caused concentration dependent effects. For 25 micrograms/ml lonidamine, there was no additive and in some cases an antagonistic effect when used with cisplatin. For higher lonidamine concentrations (75 and 100 micrograms ml), an additive effect with cisplatin (10-15 microM) was observed. This effect saturated for cisplatin concentrations of 20 microM. These data show some potential for lonidamine and cisplatin combination therapy but treatment doses and schedules will have to be identified so that the additive effect can be achieved at concentrations clinically attainable.     

Wireless,accelerometry-triggered functional electrical stimulation of the peroneal nerve in spastic paresis: A randomized,controlled pilot study

In hemiparesis, Wireless, Accelerometry-Triggered Functional Electrical Stimulation (WAFES) of the common peroneal nerve may hold intrinsic rehabilitative properties. The present pilot study analyzes WAFES against conventional therapy. Twenty adults with chronic hemiparesis (time since lesion 7(6) years; median (interquartile range)) were randomized into 2 10-week rehabilitation programs: a 45-minute (min) daily walk using WAFES (n = 10) and conventional physical therapy (CPT), 3 × 45 min per week (n = 10). The outcomes were 3D sagittal speed measurements, step length, cadence, maximal amplitude and velocity of hip, knee, and ankle during gait at free and fast speed without WAFES and clinical assessments of plantar flexor angles of shortening, spasticity, and weakness, before (D1) and after the program (W10). Kinematic and spasticity improvements occurred in the WAFES group only: (i) ankle dorsiflexion velocity (D1 versus W10, free speed, WAFES, +4(5)°/sec, p = 0.002; CPT, ?3(8)°/sec, p = 0.007; fast, WAFES, +8(6)°/sec, p = 0.03; CPT, ?1(4)°/sec, NS); (ii) maximal passive ankle dorsiflexion (WAFES,+26(85)%; CPT,+0(27)%; group-visit, p = 0.007) and knee flexion (WAFES, +13(17)%; CPT, ?1(11)%; group-visit, p = 0.006) at fast speed only; (iii) 15% plantar flexor spasticity grade reduction with WAFES. Over 10 weeks, gait training using WAFES improved ankle and knee kinematics and reduced plantar flexor spasticity compared with CPT. Studies with longer WAFES use should explore functional effects.